The field of the invention is recombinant plant viruses, especially their use as immunizing agents which carry antigenic sequences from mammalian (e.g., human) or other animal pathogens and their use as a system for increased production of polypeptides of interest.
Traditionally, successful vaccination has been dependent upon the use of live attenuated viruses or preparations of killed pathogenic organisms. These vaccines are very effective in controlling or, as in the case of smallpox, even eliminating certain infectious diseases. However, their use often present safety concerns. Subunit vaccines based on peptide or proteins derived from a pathogen are less hazardous than traditional vaccines but have generally suffered from poor immunogenicity and high expense. Moreover, current vaccines with a few exceptions must be administered parenterally. However, it is well known that most pathogens gain entry across the mucosal surfaces of the body and a mucosal immune response would therefore be more appropriate.
Both safety concerns and the desire to target mucosal tissues for more effective immunization against common pathogens dictate the need for new approaches to vaccination. For induction of a mucosal response, oral administration of antigen is appropriate, inexpensive, and safe. However, in order to efficiently immunize by the oral route, several obstacles such as degradation from low pH or proteases in the gastrointestinal GI tract, the short exposure to immune induction sites, and limited permeability must be overcome.
Recent studies demonstrate that plants and plant viruses can function as effective tools for vaccine production and delivery. Furthermore, like liposomes and microcapsules, it is expected that plant cells and plant viruses will serve as delivery vehicles providing natural protection for the antigen associated with them and enhancing the uptake of the antigen from the GI tract. Such new developing xe2x80x9cgreen system vaccinesxe2x80x9d have significant advantages over the traditional and synthetic vaccines as regards safety, deliverability via either parenteral, nasal or oral routes, and lower cost of production.
In one general aspect, the current invention is a process of delivering a fusion capsid protein (a plant virus capsid protein fused to a foreign polypeptide) to a mammal (such as a human) or other animal using recombinant tobacco mosaic virus (TMV) genetic material (TMV genetic material combined with genetic material that codes for a chimeric capsid protein, the chimeric capsid protein being capsid protein of either an alfalfa mosaic virus (AlMV) capsid protein (CP) or ilarvirus CP, fused to the foreign polypeptide) as a delivery vehicle to that mammal or other animal. A foreign polypeptide is one that does not naturally occur in either TMV, an AlMV or an ilarvirus. The fusion protein is administered to the mammal or other animal for purposes of inducing an immune response against the foreign polypeptide. In a second general aspect, the invention is a production process: the use of such a chimeric virus to express the fused coat protein (comprising either an antigenic or nonantigenic foreign protein) in a plant.